摘要
Objective: Malignant glioma is the most frequently occurring primary tumor of the central nervous system, and represents one of the most lethal malignancies. Glioma cells show a stubborn resistance to several treatments, the etiology of malignant glioma remains obscure. Yet there are currently many studies over the potential involvement of viruses in malignant gliomas. Many studies reported that HCMV products were detected in malignant glioma, and correlated to tumor grade. HCMV stimulation with pathogen-associated molecular patterns triggering activation of the transcription factors,including NF-КB, IFN regulatory factor 3(IRF3) leads to the production of proinflammatory cytokines, type I IFNs, and induction of subsequent adaptive immune responses to exert anti-virus and anti-tumor effects. In this study, USP18 regulation on TBK1-IRF3-IFNβ signaling and its effect on malignant glioma activities were investigated.Methods: HCMV AD169 was utilized to infect human astrocytes, and whole genome transcriptome profile was conducted. In clinical malignant glioma specimens, we detected the virus in frozen tumor specimens by indirect immunofluorescence or in paraffin embedded tumor tissue specimens using the high sensitive immunostaining protocols and the expression of USP18 was also detected compared to paired normal tissues. TBK1-IRF3-IFNβ signaling was detected in cultured glioma cells. Results: results showed that the virus was detected in frozen tumor specimens and we also detected high expression of USP18 compared to paired normal tissues. TBK1-IRF3-IFNβ signaling was regulated by USP18 in cultured glioma cells. Conclusion: USP18 regulated TBK1-IRF3-IFNβ signaling and had effects on malignant glioma activities, which would provide new targets on treatment of malignant glioma
Objective: Malignant glioma is the most frequently occurring primary tumor of the central nervous system, and represents one of the most lethal malignancies. Glioma cells show a stubborn resistance to several treatments, the etiology of malignant glioma remains obscure. Yet there are currently many studies over the potential involvement of viruses in malignant gliomas. Many studies reported that HCMV products were detected in malignant glioma, and correlated to tumor grade. HCMV stimulation with pathogen-associated molecular patterns triggering activation of the transcription factors,including NF-КB, IFN regulatory factor 3(IRF3) leads to the production of proinflammatory cytokines, type I IFNs, and induction of subsequent adaptive immune responses to exert anti-virus and anti-tumor effects. In this study, USP18 regulation on TBK1-IRF3-IFNβ signaling and its effect on malignant glioma activities were investigated.Methods: HCMV AD169 was utilized to infect human astrocytes, and whole genome transcriptome profile was conducted. In clinical malignant glioma specimens, we detected the virus in frozen tumor specimens by indirect immunofluorescence or in paraffin embedded tumor tissue specimens using the high sensitive immunostaining protocols and the expression of USP18 was also detected compared to paired normal tissues. TBK1-IRF3-IFNβ signaling was detected in cultured glioma cells. Results: results showed that the virus was detected in frozen tumor specimens and we also detected high expression of USP18 compared to paired normal tissues. TBK1-IRF3-IFNβ signaling was regulated by USP18 in cultured glioma cells. Conclusion: USP18 regulated TBK1-IRF3-IFNβ signaling and had effects on malignant glioma activities, which would provide new targets on treatment of malignant glioma
引文